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Use stem cells for custom blood vessels

JOHNS HOPKINS (US) — Engineers have coaxed stem cells into forming networks of new blood vessels, then successfully transplanted them into mice.

“That these vessels survive and function inside a living animal is a crucial step in getting them to medical application,” says Sravanti Kusuma, a biomedical engineering graduate student at Johns Hopkins University.

The human stem cells used in the experiment were made by reprogramming ordinary cells, so the new technique could potentially be used to make blood vessels genetically matched to individual patients and unlikely to be rejected by their immune systems, investigators say.


Human blood vessel networks, in red, grown in a lab from stem cells and then transplanted into a mouse, are seen incorporating themselves into and around networks of the mouse’s vessels, in green. (Credit: PNAS)

Custom-made blood vessel networks could help patients with burns, complications of diabetes, or other conditions that compromise blood flow.

“In demonstrating the ability to rebuild a microvascular bed in a clinically relevant manner, we have made an important step toward the construction of blood vessels for therapeutic use,” says Sharon Gerecht, associate professor of chemical and biomolecular engineering.

Blood vessels have previously been grown in the laboratory using stem cells, but barriers remained to efficiently producing the vessels and using them to treat patients.

For the latest study, published in Proceedings of the National Academy of Sciences, researchers focused on streamlining the process. Where other experiments used chemical cues to get stem cells to form cells of a single type, or to mature into a smorgasbord of cell types that the researchers would then sort through, Kusuma devised a way to get the stem cells to form the two cell types needed to build new blood vessels—and only those types.

“It makes the process quicker and more robust if you don’t have to sort through a lot of cells you don’t need to find the ones you do, or grow two batches of cells,” Kusuma says.

Elegant use of cells

A second difference from previous experiments was that instead of using adult stem cells derived from cord blood or bone marrow to construct the network of vessels, Gerecht’s group teamed with Linzhao Cheng, a professor in the Institute for Cell Engineering, to use induced pluripotent stem cells as their starting point.

Since this type of cell is made by reverse-engineering mature cells—from the skin or blood, for example—using it means that the resulting blood vessels could be tailor-made for specific patients.

“This is an elegant use of human induced pluripotent stem cells that can form multiple cell types within one kind of tissue or organ and have the same genetic background,” Cheng says.

“This study showed that in addition to being able to form blood cells and neural cells as previously shown, blood-derived human induced pluripotent stem cells can also form multiple types of vascular network cells.”

To grow the vessels, the research team put stem cells into scaffolding made of a squishy material called hydrogel. The hydrogel was loaded with chemical cues that nudged the cells to organize into a network of recognizable blood vessels made up of cells that create the network and the type that support and give vessels their structure.

This was the first time that blood vessels had been constructed from human pluripotent stem cells in synthetic material.

To learn whether the vessel-infused hydrogel would work inside a living animal, the group implanted it into mice. After two weeks, the lab-grown vessels had integrated with the mice’s own vessels; the hydrogel had begun to biodegrade and disappear as designed.

One of the next steps, Kusuma says, will be to look more closely at the 3D structures the lab-grown vessels form. Another will be to see whether the vessels can deliver blood to damaged tissues and help them recover.

The study was funded by the American Heart Association, the National Heart, Lung, and Blood Institute, the National Cancer Institute, and the National Science Foundation.

Source: Johns Hopkins University

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